1. Field of the Invention
The present invention relates to a method for producing an xcex1-aminonitrile by aerobic oxidation of a tertiary amine with a cyanide by using a transition metal catalyst.
2. Related Art Statement
In the fields of medicinal and material sciences, the necessity for the nitrogen-containing organic compounds has been increasing in recent years, and development of efficient and selective methods for constructing carbon skeletons of nitrogen-containing organic compounds has been urgently required. An xcex1-aminonitrile is obtained by cyanating carbon at a position adjacent to a nitrogen atom of a tertiary amine through catalytic oxidation with oxygen. Since this xcex1-aminonitrile is easily converted to an amino acid as well as various nitrogen-containing biologically active materials, the utility of the reaction is high.
It is known that such xcex1-aminonitriles are obtained by employing anode oxidation (J. Am. Chem. Soc. 91, 4181 (1969), a photo reaction (Tetrahedron Lett. 31, 4735 (1990), chlorine dioxide (J. Am. Chem. Soc. 110, 4829 (1988), a benzoiodine xole (Tetrahedron Lett. 36, 7975 (1995)), or cyano iodine or the like. However, the above reactions are not industrially proper methods, since these should employ special reaction apparatuses, special reaction reagents that are difficult to obtain a large amount.
The present inventors discovered a method for producing xcex1-aminonitriles by the reaction of tertiary amines with trimethylsilyl cyanide in the presence of ruthenium chloride and peracetic acid (Japanese Chemical Society No. 70 Spring Season Annual Report 3J247). However, this method since it uses relatively expensive trimethylsilyl and peracetic acid and gives many byproducts needed further improvement for an industrial process. After further investigation in view of this, the present inventors discovered a method for producing xcex1-aminonitriles from tertiary amines by using metal cyanides and hydrogen peroxide both of which are inexpensive and easily available (JP-A 11-255,729). Although this method can produce the xcex1-aminonitriles relatively inexpensively, the efficient method using molecular oxygen, a method using a safer and cheaper oxidant, has been demanded to be developed.
Having examined oxidizing agents that satisfies sufficient safety and economy for industry process, the present inventors discovered that xcex1-aminonitriles are obtained by oxidizing tertiary amines with molecular oxygen, and reached the invention based on this discovery. That is, the present invention is to provide a method for producing an xcex1-aminonitrile, comprising the step of oxidizing a tertiary amine with oxygen by using a transition metal catalyst in the presence of a cyanide.
As the tertiary amine for a starting material is preferable a tertiary amine that is represented by a general formula R1R2NCH2R3 in which R1 is a phenyl group which may be substituted, R2 is an alkyl group or a phenyl group which may be substituted, R3 is a hydrogen atom, an alkyl group or a phenyl group which may be substituted, provided that R1 and R3 or R2 and R3 may be bonded to form a nitrogen-containing ring.
(1-1) Substituting Group R1 
As the phenyl group, which may be substituted, in the substituting group R1 of the compound represented by the general formula R1R2NCH2R3, mention may be made of, for example, phenyl group, lower alkyl-substituted phenyl groups such as 2-methylphenyl group, 3-methylphenyl group and 4-methylphenyl group, halogen-substituted phenyl groups such as 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, 2-bromophenyl group, 3-bromophenyl group and 4-bromophenyl group, lower alkoxyphenyl groups such as 2-methoxyphenyl group, 3-methoxyphenyl group and 4-methoxyphenyl group, etc.
(1-2) R2, R3, etc.
As the alkyl groups for R2 and R3, mention may be made of, for example, methyl group, ethyl group, n-propyl group, i-propyl group, n-butyl group, s-butyl group, t-butyl group, pentyl group, hexyl group and cyclohexyl group. As the phenyl group which may be substituted, mention may be made of, for example, phenyl group, lower alkyl-substituted phenyl groups such as 2-methylphenyl group, 3-methylphenyl group and 4-methylphenyl group, halogen-substituted phenyl groups such as 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, 2-bromophenyl group, 3-bromophenyl group and 4-bromophenyl group, lower alkoxyphenyl groups such as 2-methoxyphenyl group, 3-methoxyphenyl group and 4-methoxyphenyl group, etc.
As the nitrogen-containing ring which is formed when R2 and R3 are bonded to each other, mention may be made of piperidine, pyrrolidine, N-phenyl-1,2,3,4-tetrahydroisoquinoline, etc. As the nitrogen-containing ring which is formed when R1 and R3 are bonded to each other, mention may be made of 1, 2, 3, 4-tetrahydroisoquinoline, etc.
As specific examples for the tertiary amines, mention may be made of N,N-dimethylaniline, N-ethyl-N-methylaniline, N,N-diethylaniline, N-phenyl-N-methylaniline, N,N,4-trimethylaniline, N,N-dimethyl-4-bromoaniline, N,N-dimethyl-4-methoxyaniline, N-phenylpiperidine, N-(4-methoxyphenyl)piperidine, N-phenyl-1,2,3,4-tetrahydroisoquinoline, 6-benzyloxy-N-phenyl-7-methoxy-1, 2,3,4-tetrahydroxyisoquinoline, etc.
As the cyanide for a starting material, alkali metal cyanides such as sodium cyanide and potassium cyanide, hydrogen cyanide or trimethylsilyl cyanide is preferred. From the reactivity and economical points of view, sodium cyanide and potassium cyanide are preferably used.
Although the use amount of the cyanide is not particularly limited, it is ordinarily 1 to 10 times in mole, preferably 1 to 3 times in mole as much as that of a substrate (tertiary amine). The cyanide may be used as it is, or in the form of a solution in which the cyanide is dissolved in a solvent mentioned later.
The xcex1-aminonitrile obtained in the present invention is preferably represented by a general formula R1R2NCH(CN)R3 in which R1 is a phenyl group which may be substituted, R2 is an alkyl group or a phenyl group which may be substituted, R3 is a hydrogen atom, an alkyl group or a phenyl group which may be substituted, provided that R1 and R3 or R2 and R3 may be bonded to form a nitrogen-containing ring. Those recited in the above (1-1) and (1-2) are employed as specific examples for the R1, R2 and R3.
As specific examples for the xcex1-aminonitrile of the general formula R1R2NCH(CN)R3 produced by the present invention, mention may be made of, for example, N-phenyl-N-methylaminoacetonitrile, N-phenyl-N-ethylamino-acetonitrile, 2-(N-ethyl-N-phenylamino)propionitrile, N,N-diphenylamino-acetonitrile, N-(4-methylphenyl)-N-methylaminoacetonitrile, N-(4-bromophenyl)-N-methylaminoacetonitrile, N-(4-methoxyphenyl)-N-methylaminoacetonitrile, 2-cyano-N-phenylpiperidine, 2-cyano-N-(4-methoxyphenyl)piperidine, 1-cyano-N-phenyl-1, 2,3,4-tetrahydroxyisoquinoline, 1-cyano-6-benzyloxy-N-phenyl-7-methoxy-1, 2,3,4-tetrahydroisoquinoline, etc.
As the transition metal catalyst used in the present invention, one or more transition metal catalysts selected from the group consisting of a ruthenium-based catalyst, a chromium-based catalyst, a manganese-based catalyst, an iron-based catalyst, a cobalt-based catalyst, a nickel-based catalyst and a palladium-based catalyst are preferred. For example, use may be made of ruthenium catalysts such as RuCl3-nH2O, n-Pr4NRuO4, Ru2(xcexc-OAc)4Cl, Ru3(xcexc-O) (xcexc-OAc)6(H2O)3, RuO2, KRuO4, RuCl2(PPh3)3, RuCl2(bpy)2, Ru(acac)3 and K4Ru(CN)6, chromium-based catalyst such as CrCl2, manganese-based catalysts such as MnCl2, iron-based catalysts such as FeCl3, cobalt-based catalysts such as CoCl2, nickel-based catalysts such as NiCl2 and palladium-based catalysts such as PdCl2. Among them, RuCl3-nH2O is preferably used. Either anhydrides or hydrates of them may be employed. The use amount of the transition metal catalyst is ordinarily not less than 0.01 mol % relative to a substrate (tertiary amine), and no value is posed upon its upper limit. However, the use amount is preferably in a range of 1 to 5 mol %.
Oxygen to be used in the present reaction may be supplied in the form of oxygen gas, a mixture of oxygen and an inert gas such as nitrogen or air, preferably at an oxygen pressure of 1 atm. Oxygen may be at a reduced or pressurized pressure.
(6-1) Solvent
A solvent may be used in the present reaction. As the solvent, hydrocarbons (hexane, heptane, toluene, benzene, etc.), halogenated hydrocarbons (methylene chloride, chloroform, 1,2-dichloroethane, chlorobenzene, etc.), ketones (acetone, etc.), esters (ethyl acetate, etc.), alcohols (methanol, ethanol, n-propanol, i-propanol, n-butanol, s-butanol, t-butanol, n-pentanol, etc.), carboxylic acids (acetic acid, propionic acid, butanoic acid, pentanoic acid, etc.), etc. These compounds may be used singly or as a mixture of two or more of them. Preferably, a mixed solvent of an alcohol and a carboxylic acid may be recited, and its mixing ratio (alcohol/carboxylic acid) is ordinarily 0.01 to 100, preferably 0.1 to 10.
(6-2) Reacting Condition
The reaction temperature is ordinarily xe2x88x9250xc2x0 C. to 100xc2x0 C., preferably 20xc2x0 C. to 100xc2x0 C., more preferably 50xc2x0 C. to 80xc2x0 C. The reaction time is longer as the reaction temperature descends, whereas it is short as the reaction temperature rises. The reaction time is appropriately determined depending upon the reacting temperature.